The present disclosure relates to an automated pipetting device, to a pipetting device positioning system comprising the pipetting device and to an in-vitro diagnostic system comprising the pipetting device positioning system.
Typical workflows in automated in vitro diagnostic systems comprise pipetting, i.e., aspirating and/or dispensing liquids, such as samples and reagents, from and/or into liquid containers, involving the use of automated pipetting devices.
An automated pipetting device normally comprises a pipette nozzle. The pipette nozzle, depending on the application, e.g., in case of susceptibility to carry-over, may comprise a reusable needle or a consumable tip.
Depending on the application, liquid containers may be loaded open or closed into an in-vitro diagnostic system. Mostly, reagent containers are closed by a cap in order to increase onboard stability by preventing evaporation, contamination and interference by external factors. Sample containers may be loaded open or closed, also depending on the application.
With closed liquid containers, pipetting of liquids contained therein becomes more complicated. Caps need to be at least temporarily removed in order to enable access of a pipette nozzle to the liquid contained therein, especially if consumable tips instead of needles are used. Opening and closing liquid containers may be technically complicated, bulky and costly if automated.
As an alternative, caps may be configured to enable a pipette nozzle, particularly a pipette needle, to access the liquid in the liquid container through the cap. Elastomeric caps may be, for example, pierced, either directly by the pipette needle or by a dedicated piercer before inserting the pipette needle. Pre-cut sections in the caps are sometimes also used in order to facilitate insertion of a pipette nozzle whereas upon removal of the pipette nozzle the cap is resiliently reclosed by itself. Pipetting through a cap has however several disadvantages. One disadvantage is that contact of the pipette nozzle with the cap can cause cross-contamination. Also, the risk of damaging the pipette nozzle is increased. Also, most techniques for detecting a level of the liquid in the liquid container, e.g., based on capacitance measurement, are hindered by the presence of a cap and/or possible traces of liquid present on the cap.
Another general problem associated with pipetting devices is a chain of mechanical and geometrical tolerances in the vertical direction. In particular, tolerances in the assembly of the pipetting device, including manual or automated coupling of the pipette nozzle, tolerances in the driving mechanism for translating the pipetting device in the vertical direction, manufacturing tolerances with respect to the dimensions of the liquid container, positioning of the liquid container within the in-vitro diagnostic system in possibly different liquid container holding positions, can result in an even larger cumulative tolerance and therefore in a relatively large imprecision in the vertical positioning of a pipette nozzle with respect to the liquid container, in particular with respect to the bottom of the liquid container.
In particular, as the liquid in the liquid container is used up and the level of liquid decreases, it is desirable to be able to position the pipette nozzle as close as possible to the bottom of the liquid container in order to minimize the dead volume.
However, because of the imprecision in the positioning of the pipette nozzle, a safety distance from the bottom of the container is maintained in order to prevent a crash of the pipette nozzle with the bottom of the liquid container, which could result in an incorrect pipetting, a damage of the pipette nozzle and/or of the liquid container and the like. As a consequence, the dead volume, i.e., the amount of liquid remaining at the bottom of the liquid container that is not used and therefore wasted can be significantly high, e.g., up to 10% of the entire liquid volume, or even more, especially for smaller liquid containers, e.g., below 20-30 mL.